Cognitive decline is correlated with brain atrophy associated with synaptic loss. For instance, alteration of synaptic efficacy in the hippocampus is an initial event in cognitive disorders such as Alzheimer's disease (AD). As synapses are the elemental unit of neural computation, the structural and functional loss of synapses are associated with impaired cognition.
Neuronal intracellular ionized Mg2+ is an important signaling molecule regulating structural and functional synaptic terminal density, with higher intracellular concentration ([Mg2+]i) generally resulting in greater structural and functional synaptic terminal density. Not only does neuronal intracellular Mg2+ promote structural synapse density and plasticity (Slutsky et al., (2010). Neuron 65(2): 165-177), but it also controls whether presynaptic terminals are functional or nonfunctional (Zhou and Liu (2015). Mol Brain 8(1): 42). Functional synapses are able to release neurotransmitters via synaptic vesicles and thus affect the post-synaptic neuron, while nonfunctional synapses are structurally present but fail to release neurotransmitters and are unable to signal to the post-synaptic neuron.